Reference

J Exp Med. DOI: 10.1084/jem.20150821 (2016)journal

Authors

Alba Azagra, Lidia Román-González, Olga Collazo, Javier Rodríguez-Ubreva, Virginia G de Yébenes, Bruna Barneda-Zahonero, Jairo Rodríguez, Manuel Castro de Moura, Joaquim Grego-Bessa, Irene Fernández-Duran, Abul B.M.M.K. Islam, Manel Esteller, Almudena R Ramiro, Esteban Ballestar and Maribel Parra

Abstract

Class IIa Histone Deacetylases (HDACs) subfamily members are tissue-specific gene repressors with crucial roles in development and differentiation processes. A prominent example is HDAC7, a class IIa HDAC that shows a lymphoid-specific expression pattern within the hematopoietic system. Here, we explored its potential role in B cell development by generating a conditional knockout mouse model. Our study demonstrates for the first time that HDAC7 deletion dramatically blocks early B cell development and gives rise to a severe lymphopenia in peripheral organs, while leading to pro-B cell lineage promiscuity. We find that HDAC7 represses myeloid and T lymphocyte genes in B cell progenitors, through interaction with myocyte enhancer factor 2C (MEFC2). In B cell progenitors HDAC7 is recruited to promoters and enhancers of target genes and its absence leads to increase enrichment of histone active marks. Our results prove that HDAC7 is a bona fide transcriptional repressor essential for B cell development.

Description

Los resultados del presente artículo demuestran que HDAC7 es un represor transcripcional crucial para el correcto desarrollo de linfocitos B. En concreto, hemos generado ratones deficientes en HDAC7 en progenitores de células B (células pro-B). Los ratones knock out condicionales en HDAC7 en linfocitos pro-B presentan un bloqueo temprano en la formación de células B. Hemos observado que las células pro-B deficientes en HDAC7 expresan genes característicos de otros linajes. A través de la interacción con el factor de transcripción MEF2C y su reclutamiento a la cromatina, HDAC7 reprime la transcripción de genes "inapropiados" asegurando la adquisición correcta de la identidad de células B.

 

Grupo Maribel Parra

 

REFERENCIA DEL GRUPO INVESTIGADOR

El grupo de Diferenciación celular del Instituto de Investigación Biomédica de Bellvitge (IDIBELL) liderado por Maribel Parra estudia los mecanismos de represión transcripcional que tienen lugar durante la diferenciación de células del sistema hematopoyético. En concreto, uno de los objetivos del grupo está enfocado al estudio del papel de la histona desacetilasa HDAC7 en la formación de linfocitos B y como su desregulación puede conllevar al desarrollo de enfermedades hematológicas como la leucemia y los linfomas.

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